A Multi-part, Double Blind Study to Assess Safety, Tolerability and Efficacy of Tropifexor (LJN452) in PBC Patients

A Multi-part, Randomized, Double-blind, Placebo-controlled Study to Assess the Safety, Tolerability and Efficacy of Tropifexor (LJN452) in Patients With Primary Biliary Cholangitis

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02516605

Enrollment

Registered

2015-08-06

Start date

2015-09-09

Completion date

2018-08-02

Last updated

2021-01-05

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Primary Biliary Cholangitis

Keywords

Primary Biliary Cirrhosis, PBC, Primary Biliary Cholangitis

Brief summary

A multi-part study to assess safety, tolerability and efficacy of tropifexor (LJN452) in patients with primary biliary cholangitis

Interventions

DRUGPart 1: LJN452

LJN452 capsules administered once daily for 28 days

DRUGPart 1: Placebo

Matching placebo capsules administered once daily for 28 days

DRUGPart 2: LJN452 Dose level 1

LJN452 capsules administered once a day for 12 weeks

DRUGPart 2: Placebo

Matching placebo to LJN452 administered once a day for 12 weeks

DRUGPart 2: LJN452 Dose level 2

LJN452

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Caregiver, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Age ≥ 18 years * Diagnosis of PBC as demonstrated by the presence of at least 2 of the following 3 diagnostic criteria: * History of alkaline phosphatase (ALP) elevated above upper limit of normal (ULN) for at least 6 months * Positive antimitochondrial antibodies (AMA) titer or if AMA negative or in low titer (\<1:80) PBC specific antibodies (anti-GP210 and/or anti-SP100 and/or antibodies against the major M2 components (PDC-E2, 2-oxo-glutaric acid dehydrogenase complex)) * Previous liver biopsy findings consistent with PBC * At least 1 of the following markers of disease severity: * ALP ≥ 1.67 × ULN * Total bilirubin \> ULN but \< 1.5 × ULN * In addition, patients must meet the following biochemical criteria at enrollment: * Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤ 5 × ULN * Total bilirubin ≤ 1.5 × ULN * INR ≤ ULN * Taking UDCA for at least 12 months, or for at least 6 months and has reached maximal response to UDCA with a plateau in alkaline phosphatase, with no changes in dose for ≥ 3 months prior to Day 1. * Patients must weigh at least 40 kg to participate in the study, and must have a body mass index (BMI) within the range of 18 - 40 kg/m2. BMI = Body weight (kg) / \[Height (m)\]2

Exclusion criteria

* Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception for 30 days before randomization, during dosing and for 30 days following the end of treatment. * Presence of other concomitant liver diseases. * Cirrhosis with complications, including history or presence of: * Variceal bleed * Uncontrolled ascites * Encephalopathy * Spontaneous bacterial peritonitis * Significant hepatic impairment as defined by Child-Pugh classification of B or C, history of liver transplantation, current placement on a liver transplant list or current Model for End Stage Liver Disease (MELD) score ≥15. * History of conditions that may cause increases in ALP (e.g., Paget's disease). * Use of investigational drugs, or immunosuppressive drugs at the time of enrollment, or within 5 half-lives, or 30 days of randomization, whichever is longer; or longer if required by local regulations. Use of high dose oral steroids to treat co-morbid conditions (e.g., airways disease) will be allowed but must be properly documented as such in concomitant medications. * Currently taking obeticholic acid or have taken obeticholic acid within 30 days of randomization * Previous participation in CLJN452X2201 and received study medication within three months of randomization (or longer if required by local regulations).

Design outcomes

Primary

Measure	Time frame	Description
Haemoglobin	Screening, Baseline, day 1, day 7, day 14, day 21, day 28, day 56, day 84	Hematology panel for safety laboratory assessments.
Fold Change in Serum Gamma-glutamyl Transferase (GGT)	Baseline to Day 28	Fold change in serum gamma-glutamyl transferase (GGT) from baseline to Day 28
Blood Pressure	Screening, Baseline, day 1, day 7, day 14, day 21, day 28, day 56, day 84	Vital signs - Systolic Blood pressure
Pulse Rate	Screening, Baseline, day 1, day 7, day 14, day 21, day 28, day 56, day 84	Vital signs
Body Temperature	Screening, Baseline, day 1, day 7, day 14, day 21, day 28, day 56, day 84	Vital signs
ECG - Heart Rate	Screening, Baseline, day 1, day 28	Electrocardiogram (ECG)
ECG Intervals - PR Interval	Screening, Baseline, day 1, day 28	Electrocardiogram (ECG)

Secondary

Measure	Time frame	Description
Plasma PK Parameter - Cmax	Day 1, Day 28	Tropifexor levels were determined in plasma using a validated LC-MS/MS method. Cmax=The observed maximum plasma concentration following drug administration \[mass /volume\]
Plasma PK Parameter - Tmax	Day 1, Day 28	Tropifexor levels were determined in plasma using a validated LC-MS/MS method. Tmax = The time to reach the maximum concentration after drug administration \[time\]
Changes From Baseline in Total PBC-40 Score	Baseline, Day 28, Day 56, Day 84	Baseline is defined as the latest available predose value. The PBC-40 is a paper-based, patient-derived, disease-specific health-related quality of life (HRQOL) patient reported outcome (PRO) measure which was developed and validated for use in PBC patients (Jacoby et al 2005). It consists of 40 questions arranged in 6 domains with between 3 and 11 questions in each domain. Each question is scored from 1 to 5 in increasing order of severity. All questions within a domain are summed and all domain totals are summed to obtain a total score. The total score range is between a minimum of 40 and a maximum of 200. Higher scores represent a poorer quality of life. The median difference from baseline in total sum score for each treatment group is presented.
Change From Baseline in Itch Subdomain of PBC-40 Score	Baseline, Day 28, Day 56, Day 84	Baseline is defined as the latest available predose value. The PBC-40 is a paper-based, patient-derived, disease-specific health-related quality of life (HRQOL) patient reported outcome (PRO) measure which was developed and validated for use in PBC patients (Jacoby et al 2005). It consists of 40 questions arranged in 6 domains with between 3 and 11 questions in each domain. Each question is scored from 1 to 5 in increasing order of severity. This dataset focuses on the itch subdomain which consists of 3 questions. These 3 questions within the itch subdomain are summed to obtain a total score for the itch subdomain. The total score range is between a minimum of 3 and a maximum of 15. Higher scores represent a poorer quality of life. The median change from baseline in total itch subdomain score in each treatment group is presented.
Change From Baseline in Global Itch Visual Analogue Scale (VAS)	Day 7, Day 14, Day 21, Day 28, Day 56, and Day 84	Baseline is defined as the latest available predose value. The Global Itch Visual Analogue Scale, a 100 mm visual analogue scale (VAS), was used to assess the severity of patients itch (ranging from 0 = none at all to 100 = the worst imaginable itch). The score range is between a minimum of 0 and a maximum of 100. The score (distance in mm from left) on the VAS was recorded by the patient marking with a line and used to test for an effect of tropifexor over placebo. The mean change from baseline in itch VAS score in each treatment group is presented.
Plasma PK Parameter - AUC 0-8h	Day 1, Day 28	Tropifexor levels were determined in plasma using a validated LC-MS/MS method. AUC0-t=The area under the plasma concentration-time curve from time zero to time 't' where t is a defined time point after administration \[mass x time / volume\]

Countries

Canada, Germany, Poland, Russia, United Kingdom, United States

Participant flow

Pre-assignment details

This study comprised of an escalating multiple dose design in PBC patients with incomplete biochemical response to, but still taking, ursodeoxycholic acid (UDCA).

Participants by arm

Arm	Count
LJN452 - 0.03 mg qd Tropifexor 0.03 mg daily for 28 days	11
LJN452 - 0.06 mg qd Tropifexor 0.06 mg daily for 28 days	9
LJN452 - 0.09 mg qd Tropifexor 0.09 mg daily for 28 days	12
LJN452 - 0.15 mg qd Tropifexor 0.15 mg daily for 28 days	8
Placebo qd Tropifexor placebo daily for 28 days	21
Total	61

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003	FG004
Overall Study	Protocol Violation	0	0	0	0	1
Overall Study	Withdrawal by Subject	0	0	0	1	0

Baseline characteristics

Characteristic	LJN452 - 0.03 mg qd	LJN452 - 0.06 mg qd	LJN452 - 0.09 mg qd	LJN452 - 0.15 mg qd	Placebo qd	Total
Age, Continuous	58.6 years STANDARD_DEVIATION 12.42	57.9 years STANDARD_DEVIATION 11.21	53.6 years STANDARD_DEVIATION 7.42	57.4 years STANDARD_DEVIATION 13.81	53.7 years STANDARD_DEVIATION 10.19	55.7 years STANDARD_DEVIATION 10.7
Race/Ethnicity, Customized Asian	0 participants	0 participants	0 participants	0 participants	1 participants	1 participants
Race/Ethnicity, Customized Caucasian	10 participants	8 participants	12 participants	8 participants	19 participants	57 participants
Race/Ethnicity, Customized Other	1 participants	1 participants	0 participants	0 participants	1 participants	3 participants
Sex: Female, Male Female	11 Participants	7 Participants	12 Participants	8 Participants	21 Participants	59 Participants
Sex: Female, Male Male	0 Participants	2 Participants	0 Participants	0 Participants	0 Participants	2 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk
deaths Total, all-cause mortality	0 / 11	0 / 9	0 / 12	0 / 8	0 / 21
other Total, other adverse events	9 / 11	8 / 9	11 / 12	8 / 8	16 / 21
serious Total, serious adverse events	0 / 11	0 / 9	0 / 12	0 / 8	0 / 21

Outcome results

Primary

Blood Pressure

Vital signs - Systolic Blood pressure

Time frame: Screening, Baseline, day 1, day 7, day 14, day 21, day 28, day 56, day 84

Population: Safety Analysis Set

Arm	Measure	Group	Value (MEAN)	Dispersion
LJN452 - 0.03 mg qd	Blood Pressure	Day 7	127.2 mm Hg	Standard Deviation 20.18
LJN452 - 0.03 mg qd	Blood Pressure	Day 1	129.6 mm Hg	Standard Deviation 20.48
LJN452 - 0.03 mg qd	Blood Pressure	Day 84	131.3 mm Hg	Standard Deviation 16.04
LJN452 - 0.03 mg qd	Blood Pressure	Baseline	124.7 mm Hg	Standard Deviation 17.66
LJN452 - 0.03 mg qd	Blood Pressure	Day 56	121.4 mm Hg	Standard Deviation 10.76
LJN452 - 0.03 mg qd	Blood Pressure	Day 14	122.4 mm Hg	Standard Deviation 16.3
LJN452 - 0.03 mg qd	Blood Pressure	Day 21	121.5 mm Hg	Standard Deviation 11.25
LJN452 - 0.03 mg qd	Blood Pressure	Day 28	118.0 mm Hg	Standard Deviation 11.22
LJN452 - 0.03 mg qd	Blood Pressure	Screening	122.5 mm Hg	Standard Deviation 12.21
LJN452 - 0.06 mg qd	Blood Pressure	Day 56	125.4 mm Hg	Standard Deviation 18.48
LJN452 - 0.06 mg qd	Blood Pressure	Day 14	124.6 mm Hg	Standard Deviation 20.67
LJN452 - 0.06 mg qd	Blood Pressure	Day 21	126.3 mm Hg	Standard Deviation 27.65
LJN452 - 0.06 mg qd	Blood Pressure	Screening	125.8 mm Hg	Standard Deviation 11.79
LJN452 - 0.06 mg qd	Blood Pressure	Baseline	128.4 mm Hg	Standard Deviation 13.83
LJN452 - 0.06 mg qd	Blood Pressure	Day 84	124.6 mm Hg	Standard Deviation 15.77
LJN452 - 0.06 mg qd	Blood Pressure	Day 28	127.1 mm Hg	Standard Deviation 28.55
LJN452 - 0.06 mg qd	Blood Pressure	Day 1	122.4 mm Hg	Standard Deviation 20.24
LJN452 - 0.06 mg qd	Blood Pressure	Day 7	123.7 mm Hg	Standard Deviation 13.04
LJN452 - 0.09 mg qd	Blood Pressure	Screening	129.3 mm Hg	Standard Deviation 14.42
LJN452 - 0.09 mg qd	Blood Pressure	Day 7	125.6 mm Hg	Standard Deviation 14.22
LJN452 - 0.09 mg qd	Blood Pressure	Day 1	119.9 mm Hg	Standard Deviation 11.84
LJN452 - 0.09 mg qd	Blood Pressure	Day 84	122.3 mm Hg	Standard Deviation 7.7
LJN452 - 0.09 mg qd	Blood Pressure	Day 28	121.4 mm Hg	Standard Deviation 12.82
LJN452 - 0.09 mg qd	Blood Pressure	Day 56	121.5 mm Hg	Standard Deviation 11.55
LJN452 - 0.09 mg qd	Blood Pressure	Baseline	122.0 mm Hg	Standard Deviation 18.18
LJN452 - 0.09 mg qd	Blood Pressure	Day 14	127.1 mm Hg	Standard Deviation 16.45
LJN452 - 0.09 mg qd	Blood Pressure	Day 21	123.9 mm Hg	Standard Deviation 13.14
LJN452 - 0.15 mg qd	Blood Pressure	Day 84	130.4 mm Hg	Standard Deviation 25.51
LJN452 - 0.15 mg qd	Blood Pressure	Day 56	129.1 mm Hg	Standard Deviation 26.45
LJN452 - 0.15 mg qd	Blood Pressure	Screening	129.5 mm Hg	Standard Deviation 17.42
LJN452 - 0.15 mg qd	Blood Pressure	Baseline	132.3 mm Hg	Standard Deviation 18.09
LJN452 - 0.15 mg qd	Blood Pressure	Day 1	129.1 mm Hg	Standard Deviation 25.12
LJN452 - 0.15 mg qd	Blood Pressure	Day 7	128.0 mm Hg	Standard Deviation 26.58
LJN452 - 0.15 mg qd	Blood Pressure	Day 14	127.3 mm Hg	Standard Deviation 12.45
LJN452 - 0.15 mg qd	Blood Pressure	Day 21	124.0 mm Hg	Standard Deviation 14.23
LJN452 - 0.15 mg qd	Blood Pressure	Day 28	126.0 mm Hg	Standard Deviation 7.71
Pooled Placebo	Blood Pressure	Day 84	123.6 mm Hg	Standard Deviation 19.09
Pooled Placebo	Blood Pressure	Day 21	124.5 mm Hg	Standard Deviation 19.8
Pooled Placebo	Blood Pressure	Day 1	123.0 mm Hg	Standard Deviation 21.84
Pooled Placebo	Blood Pressure	Baseline	118.7 mm Hg	Standard Deviation 12.76
Pooled Placebo	Blood Pressure	Screening	123.0 mm Hg	Standard Deviation 15.4
Pooled Placebo	Blood Pressure	Day 56	123.8 mm Hg	Standard Deviation 19.74
Pooled Placebo	Blood Pressure	Day 28	120.1 mm Hg	Standard Deviation 22.38
Pooled Placebo	Blood Pressure	Day 14	118.7 mm Hg	Standard Deviation 12.88
Pooled Placebo	Blood Pressure	Day 7	120.9 mm Hg	Standard Deviation 19.57

Primary

Body Temperature

Vital signs

Time frame: Screening, Baseline, day 1, day 7, day 14, day 21, day 28, day 56, day 84

Population: Safety Analysis Set

Arm	Measure	Group	Value (MEAN)	Dispersion
LJN452 - 0.03 mg qd	Body Temperature	day 56	36.527 Celsius	Standard Deviation 0.2102
LJN452 - 0.03 mg qd	Body Temperature	day 84	36.482 Celsius	Standard Deviation 0.2483
LJN452 - 0.03 mg qd	Body Temperature	day 14	36.516 Celsius	Standard Deviation 0.1793
LJN452 - 0.03 mg qd	Body Temperature	Screening	36.605 Celsius	Standard Deviation 0.2813
LJN452 - 0.03 mg qd	Body Temperature	baseline	36.582 Celsius	Standard Deviation 0.296
LJN452 - 0.03 mg qd	Body Temperature	day 7	36.582 Celsius	Standard Deviation 0.204
LJN452 - 0.03 mg qd	Body Temperature	day 1	36.436 Celsius	Standard Deviation 0.3139
LJN452 - 0.03 mg qd	Body Temperature	day 21	36.500 Celsius	Standard Deviation 0.249
LJN452 - 0.03 mg qd	Body Temperature	day 28	36.382 Celsius	Standard Deviation 0.2228
LJN452 - 0.06 mg qd	Body Temperature	day 28	36.444 Celsius	Standard Deviation 0.2128
LJN452 - 0.06 mg qd	Body Temperature	baseline	36.644 Celsius	Standard Deviation 0.2128
LJN452 - 0.06 mg qd	Body Temperature	day 56	36.500 Celsius	Standard Deviation 0.2179
LJN452 - 0.06 mg qd	Body Temperature	day 21	36.267 Celsius	Standard Deviation 0.4637
LJN452 - 0.06 mg qd	Body Temperature	Screening	36.567 Celsius	Standard Deviation 0.2
LJN452 - 0.06 mg qd	Body Temperature	day 7	36.533 Celsius	Standard Deviation 0.1323
LJN452 - 0.06 mg qd	Body Temperature	day 14	36.444 Celsius	Standard Deviation 0.2007
LJN452 - 0.06 mg qd	Body Temperature	day 84	36.500 Celsius	Standard Deviation 0.15
LJN452 - 0.06 mg qd	Body Temperature	day 1	36.537 Celsius	Standard Deviation 0.3076
LJN452 - 0.09 mg qd	Body Temperature	day 28	36.308 Celsius	Standard Deviation 0.3397
LJN452 - 0.09 mg qd	Body Temperature	day 14	36.291 Celsius	Standard Deviation 0.4109
LJN452 - 0.09 mg qd	Body Temperature	Screening	36.424 Celsius	Standard Deviation 0.3429
LJN452 - 0.09 mg qd	Body Temperature	day 1	36.482 Celsius	Standard Deviation 0.2636
LJN452 - 0.09 mg qd	Body Temperature	baseline	36.398 Celsius	Standard Deviation 0.3385
LJN452 - 0.09 mg qd	Body Temperature	day 7	36.258 Celsius	Standard Deviation 0.3965
LJN452 - 0.09 mg qd	Body Temperature	day 21	36.308 Celsius	Standard Deviation 0.3288
LJN452 - 0.09 mg qd	Body Temperature	day 56	36.350 Celsius	Standard Deviation 0.4602
LJN452 - 0.09 mg qd	Body Temperature	day 84	36.383 Celsius	Standard Deviation 0.298
LJN452 - 0.15 mg qd	Body Temperature	day 14	36.500 Celsius	Standard Deviation 0.1826
LJN452 - 0.15 mg qd	Body Temperature	day 84	36.638 Celsius	Standard Deviation 0.1506
LJN452 - 0.15 mg qd	Body Temperature	day 56	36.443 Celsius	Standard Deviation 0.3309
LJN452 - 0.15 mg qd	Body Temperature	day 1	36.575 Celsius	Standard Deviation 0.1982
LJN452 - 0.15 mg qd	Body Temperature	day 21	36.433 Celsius	Standard Deviation 0.1966
LJN452 - 0.15 mg qd	Body Temperature	Screening	36.650 Celsius	Standard Deviation 0.1604
LJN452 - 0.15 mg qd	Body Temperature	day 28	36.520 Celsius	Standard Deviation 0.295
LJN452 - 0.15 mg qd	Body Temperature	day 7	36.600 Celsius	Standard Deviation 0.1195
LJN452 - 0.15 mg qd	Body Temperature	baseline	36.638 Celsius	Standard Deviation 0.1506
Pooled Placebo	Body Temperature	day 84	36.295 Celsius	Standard Deviation 0.4248
Pooled Placebo	Body Temperature	day 1	36.390 Celsius	Standard Deviation 0.4867
Pooled Placebo	Body Temperature	day 7	36.345 Celsius	Standard Deviation 0.4639
Pooled Placebo	Body Temperature	Screening	36.460 Celsius	Standard Deviation 0.45
Pooled Placebo	Body Temperature	baseline	36.376 Celsius	Standard Deviation 0.5118
Pooled Placebo	Body Temperature	day 14	36.310 Celsius	Standard Deviation 0.4576
Pooled Placebo	Body Temperature	day 21	36.455 Celsius	Standard Deviation 0.4236
Pooled Placebo	Body Temperature	day 28	36.380 Celsius	Standard Deviation 0.4047
Pooled Placebo	Body Temperature	day 56	36.285 Celsius	Standard Deviation 0.4246

Primary

ECG - Heart Rate

Electrocardiogram (ECG)

Time frame: Screening, Baseline, day 1, day 28

Population: Safety Analysis Set

Arm	Measure	Group	Value (MEAN)	Dispersion
LJN452 - 0.03 mg qd	ECG - Heart Rate	Screening	65.8 bpm	Standard Deviation 11.32
LJN452 - 0.03 mg qd	ECG - Heart Rate	Baseline	60.5 bpm	Standard Deviation 8.99
LJN452 - 0.03 mg qd	ECG - Heart Rate	Day 1	61.5 bpm	Standard Deviation 11.16
LJN452 - 0.03 mg qd	ECG - Heart Rate	Day 28	60.5 bpm	Standard Deviation 11.39
LJN452 - 0.06 mg qd	ECG - Heart Rate	Screening	61.8 bpm	Standard Deviation 9.97
LJN452 - 0.06 mg qd	ECG - Heart Rate	Day 28	65.2 bpm	Standard Deviation 11.95
LJN452 - 0.06 mg qd	ECG - Heart Rate	Baseline	61.4 bpm	Standard Deviation 8.75
LJN452 - 0.06 mg qd	ECG - Heart Rate	Day 1	63.4 bpm	Standard Deviation 11.17
LJN452 - 0.09 mg qd	ECG - Heart Rate	Day 28	63.5 bpm	Standard Deviation 9.95
LJN452 - 0.09 mg qd	ECG - Heart Rate	Baseline	64.6 bpm	Standard Deviation 7.95
LJN452 - 0.09 mg qd	ECG - Heart Rate	Day 1	63.9 bpm	Standard Deviation 8.21
LJN452 - 0.09 mg qd	ECG - Heart Rate	Screening	67.3 bpm	Standard Deviation 5.58
LJN452 - 0.15 mg qd	ECG - Heart Rate	Screening	67.8 bpm	Standard Deviation 6.54
LJN452 - 0.15 mg qd	ECG - Heart Rate	Baseline	67.9 bpm	Standard Deviation 6.45
LJN452 - 0.15 mg qd	ECG - Heart Rate	Day 28	65.8 bpm	Standard Deviation 4.55
LJN452 - 0.15 mg qd	ECG - Heart Rate	Day 1	66.9 bpm	Standard Deviation 11.97
Pooled Placebo	ECG - Heart Rate	Day 28	60.8 bpm	Standard Deviation 7.03
Pooled Placebo	ECG - Heart Rate	Day 1	63.5 bpm	Standard Deviation 7.12
Pooled Placebo	ECG - Heart Rate	Baseline	63.8 bpm	Standard Deviation 9.41
Pooled Placebo	ECG - Heart Rate	Screening	63.4 bpm	Standard Deviation 9.35

Primary

ECG Intervals - PR Interval

Electrocardiogram (ECG)

Time frame: Screening, Baseline, day 1, day 28

Population: Safety Analysis Set

Arm	Measure	Group	Value (MEAN)	Dispersion
LJN452 - 0.03 mg qd	ECG Intervals - PR Interval	Screening	159.2 msec	Standard Deviation 27.34
LJN452 - 0.03 mg qd	ECG Intervals - PR Interval	Baseline	165.8 msec	Standard Deviation 20.81
LJN452 - 0.03 mg qd	ECG Intervals - PR Interval	Day 1	165.5 msec	Standard Deviation 21.76
LJN452 - 0.03 mg qd	ECG Intervals - PR Interval	Day 28	164.9 msec	Standard Deviation 19.75
LJN452 - 0.06 mg qd	ECG Intervals - PR Interval	Screening	158.0 msec	Standard Deviation 23.71
LJN452 - 0.06 mg qd	ECG Intervals - PR Interval	Day 28	157.1 msec	Standard Deviation 26.7
LJN452 - 0.06 mg qd	ECG Intervals - PR Interval	Baseline	156.2 msec	Standard Deviation 18.99
LJN452 - 0.06 mg qd	ECG Intervals - PR Interval	Day 1	162.9 msec	Standard Deviation 27.06
LJN452 - 0.09 mg qd	ECG Intervals - PR Interval	Day 28	180.4 msec	Standard Deviation 31.63
LJN452 - 0.09 mg qd	ECG Intervals - PR Interval	Baseline	175.0 msec	Standard Deviation 34.96
LJN452 - 0.09 mg qd	ECG Intervals - PR Interval	Day 1	175.7 msec	Standard Deviation 28.29
LJN452 - 0.09 mg qd	ECG Intervals - PR Interval	Screening	172.0 msec	Standard Deviation 24.12
LJN452 - 0.15 mg qd	ECG Intervals - PR Interval	Screening	159.9 msec	Standard Deviation 17.24
LJN452 - 0.15 mg qd	ECG Intervals - PR Interval	Baseline	152.0 msec	Standard Deviation 22.21
LJN452 - 0.15 mg qd	ECG Intervals - PR Interval	Day 28	155.4 msec	Standard Deviation 23.51
LJN452 - 0.15 mg qd	ECG Intervals - PR Interval	Day 1	160.0 msec	Standard Deviation 20.32
Pooled Placebo	ECG Intervals - PR Interval	Day 28	160.2 msec	Standard Deviation 28.7
Pooled Placebo	ECG Intervals - PR Interval	Day 1	161.6 msec	Standard Deviation 20.28
Pooled Placebo	ECG Intervals - PR Interval	Baseline	160.3 msec	Standard Deviation 19.77
Pooled Placebo	ECG Intervals - PR Interval	Screening	162.6 msec	Standard Deviation 19.03

Primary

Fold Change in Serum Gamma-glutamyl Transferase (GGT)

Fold change in serum gamma-glutamyl transferase (GGT) from baseline to Day 28

Time frame: Baseline to Day 28

Population: The PD analysis set included all subjects with any available PD data and no protocol deviations with relevant impact on PD data.

Arm	Measure	Value (MEAN)
LJN452 - 0.03 mg qd	Fold Change in Serum Gamma-glutamyl Transferase (GGT)	0.74 fold-change
LJN452 - 0.06 mg qd	Fold Change in Serum Gamma-glutamyl Transferase (GGT)	0.41 fold-change
LJN452 - 0.09 mg qd	Fold Change in Serum Gamma-glutamyl Transferase (GGT)	0.28 fold-change
LJN452 - 0.15 mg qd	Fold Change in Serum Gamma-glutamyl Transferase (GGT)	0.31 fold-change
Pooled Placebo	Fold Change in Serum Gamma-glutamyl Transferase (GGT)	0.86 fold-change

p-value: 0.29390% CI: [0.68, 1.09]ANCOVA

p-value: <0.00190% CI: [0.37, 0.6]ANCOVA

p-value: <0.00190% CI: [0.26, 0.4]ANCOVA

p-value: <0.00190% CI: [0.27, 0.47]ANCOVA

Primary

Haemoglobin

Hematology panel for safety laboratory assessments.

Time frame: Screening, Baseline, day 1, day 7, day 14, day 21, day 28, day 56, day 84

Population: Safety Analysis Set

Arm	Measure	Group	Value (MEAN)	Dispersion
LJN452 - 0.03 mg qd	Haemoglobin	day 84	126.5 g/L	Standard Deviation 8.78
LJN452 - 0.03 mg qd	Haemoglobin	day 14	126.5 g/L	Standard Deviation 9.83
LJN452 - 0.03 mg qd	Haemoglobin	baseline	126.5 g/L	Standard Deviation 8.58
LJN452 - 0.03 mg qd	Haemoglobin	day 21	127.5 g/L	Standard Deviation 8.32
LJN452 - 0.03 mg qd	Haemoglobin	day 56	126.7 g/L	Standard Deviation 6.96
LJN452 - 0.03 mg qd	Haemoglobin	day 1	124.7 g/L	Standard Deviation 8.21
LJN452 - 0.03 mg qd	Haemoglobin	day 28	125.3 g/L	Standard Deviation 9.18
LJN452 - 0.03 mg qd	Haemoglobin	day 7	124.0 g/L	Standard Deviation 8.23
LJN452 - 0.03 mg qd	Haemoglobin	Screening	127.9 g/L	Standard Deviation 9.24
LJN452 - 0.06 mg qd	Haemoglobin	day 28	127.1 g/L	Standard Deviation 14.67
LJN452 - 0.06 mg qd	Haemoglobin	day 21	128.0 g/L	Standard Deviation 13.49
LJN452 - 0.06 mg qd	Haemoglobin	day 7	128.8 g/L	Standard Deviation 16.97
LJN452 - 0.06 mg qd	Haemoglobin	day 14	127.3 g/L	Standard Deviation 12.64
LJN452 - 0.06 mg qd	Haemoglobin	day 1	132.9 g/L	Standard Deviation 10.05
LJN452 - 0.06 mg qd	Haemoglobin	day 84	124.9 g/L	Standard Deviation 9.75
LJN452 - 0.06 mg qd	Haemoglobin	baseline	127.4 g/L	Standard Deviation 11.85
LJN452 - 0.06 mg qd	Haemoglobin	Screening	125.6 g/L	Standard Deviation 11.7
LJN452 - 0.06 mg qd	Haemoglobin	day 56	125.8 g/L	Standard Deviation 11.15
LJN452 - 0.09 mg qd	Haemoglobin	day 21	130.5 g/L	Standard Deviation 10.4
LJN452 - 0.09 mg qd	Haemoglobin	Screening	130.5 g/L	Standard Deviation 9.73
LJN452 - 0.09 mg qd	Haemoglobin	baseline	130.5 g/L	Standard Deviation 11.9
LJN452 - 0.09 mg qd	Haemoglobin	day 1	127.0 g/L	Standard Deviation 9.03
LJN452 - 0.09 mg qd	Haemoglobin	day 7	132.4 g/L	Standard Deviation 10.66
LJN452 - 0.09 mg qd	Haemoglobin	day 14	128.6 g/L	Standard Deviation 7.82
LJN452 - 0.09 mg qd	Haemoglobin	day 28	129.6 g/L	Standard Deviation 10.02
LJN452 - 0.09 mg qd	Haemoglobin	day 56	128.6 g/L	Standard Deviation 10.63
LJN452 - 0.09 mg qd	Haemoglobin	day 84	125.9 g/L	Standard Deviation 11.19
LJN452 - 0.15 mg qd	Haemoglobin	day 7	134.0 g/L	Standard Deviation 8.75
LJN452 - 0.15 mg qd	Haemoglobin	day 21	134.2 g/L	Standard Deviation 9.91
LJN452 - 0.15 mg qd	Haemoglobin	day 1	133.1 g/L	Standard Deviation 11.37
LJN452 - 0.15 mg qd	Haemoglobin	day 28	136.4 g/L	Standard Deviation 13.5
LJN452 - 0.15 mg qd	Haemoglobin	baseline	134.6 g/L	Standard Deviation 13.24
LJN452 - 0.15 mg qd	Haemoglobin	day 84	131.1 g/L	Standard Deviation 10.91
LJN452 - 0.15 mg qd	Haemoglobin	day 56	133.6 g/L	Standard Deviation 12
LJN452 - 0.15 mg qd	Haemoglobin	Screening	133.9 g/L	Standard Deviation 12.7
LJN452 - 0.15 mg qd	Haemoglobin	day 14	135.4 g/L	Standard Deviation 13.5
Pooled Placebo	Haemoglobin	Screening	132.2 g/L	Standard Deviation 8.81
Pooled Placebo	Haemoglobin	day 7	128.6 g/L	Standard Deviation 9.18
Pooled Placebo	Haemoglobin	day 21	128.8 g/L	Standard Deviation 10.79
Pooled Placebo	Haemoglobin	day 1	126.8 g/L	Standard Deviation 7.63
Pooled Placebo	Haemoglobin	day 14	128.7 g/L	Standard Deviation 10.84
Pooled Placebo	Haemoglobin	day 84	129.3 g/L	Standard Deviation 9.24
Pooled Placebo	Haemoglobin	day 56	129.3 g/L	Standard Deviation 11.39
Pooled Placebo	Haemoglobin	day 28	125.7 g/L	Standard Deviation 9.71
Pooled Placebo	Haemoglobin	baseline	131.3 g/L	Standard Deviation 8.02

Primary

Pulse Rate

Vital signs

Time frame: Screening, Baseline, day 1, day 7, day 14, day 21, day 28, day 56, day 84

Population: Safety Analysis Set

Arm	Measure	Group	Value (MEAN)	Dispersion
LJN452 - 0.03 mg qd	Pulse Rate	Day 84	65.6 bpm	Standard Deviation 10.24
LJN452 - 0.03 mg qd	Pulse Rate	Day 14	62.9 bpm	Standard Deviation 10.03
LJN452 - 0.03 mg qd	Pulse Rate	Baseline	64.3 bpm	Standard Deviation 7.79
LJN452 - 0.03 mg qd	Pulse Rate	Day 21	65.5 bpm	Standard Deviation 8.26
LJN452 - 0.03 mg qd	Pulse Rate	Day 56	66.8 bpm	Standard Deviation 9.64
LJN452 - 0.03 mg qd	Pulse Rate	Day 1	67.7 bpm	Standard Deviation 11.93
LJN452 - 0.03 mg qd	Pulse Rate	Day 28	65.5 bpm	Standard Deviation 10.83
LJN452 - 0.03 mg qd	Pulse Rate	Day 7	65.2 bpm	Standard Deviation 9.98
LJN452 - 0.03 mg qd	Pulse Rate	Screening	68.6 bpm	Standard Deviation 10.63
LJN452 - 0.06 mg qd	Pulse Rate	Day 28	68.9 bpm	Standard Deviation 10.6
LJN452 - 0.06 mg qd	Pulse Rate	Day 21	65.8 bpm	Standard Deviation 11.18
LJN452 - 0.06 mg qd	Pulse Rate	Day 7	66.8 bpm	Standard Deviation 11.31
LJN452 - 0.06 mg qd	Pulse Rate	Day 14	64.8 bpm	Standard Deviation 8.09
LJN452 - 0.06 mg qd	Pulse Rate	Day 1	64.2 bpm	Standard Deviation 8.07
LJN452 - 0.06 mg qd	Pulse Rate	Day 84	64.0 bpm	Standard Deviation 9.11
LJN452 - 0.06 mg qd	Pulse Rate	Baseline	64.1 bpm	Standard Deviation 8.7
LJN452 - 0.06 mg qd	Pulse Rate	Screening	61.2 bpm	Standard Deviation 7.05
LJN452 - 0.06 mg qd	Pulse Rate	Day 56	67.7 bpm	Standard Deviation 7.53
LJN452 - 0.09 mg qd	Pulse Rate	Day 21	73.2 bpm	Standard Deviation 8.43
LJN452 - 0.09 mg qd	Pulse Rate	Screening	75.3 bpm	Standard Deviation 8.22
LJN452 - 0.09 mg qd	Pulse Rate	Baseline	70.8 bpm	Standard Deviation 8.63
LJN452 - 0.09 mg qd	Pulse Rate	Day 1	69.7 bpm	Standard Deviation 7.5
LJN452 - 0.09 mg qd	Pulse Rate	Day 7	70.1 bpm	Standard Deviation 11.64
LJN452 - 0.09 mg qd	Pulse Rate	Day 14	70.5 bpm	Standard Deviation 14.16
LJN452 - 0.09 mg qd	Pulse Rate	Day 28	68.5 bpm	Standard Deviation 9.01
LJN452 - 0.09 mg qd	Pulse Rate	Day 56	69.7 bpm	Standard Deviation 8.17
LJN452 - 0.09 mg qd	Pulse Rate	Day 84	70.2 bpm	Standard Deviation 8.14
LJN452 - 0.15 mg qd	Pulse Rate	Day 7	73.5 bpm	Standard Deviation 8.33
LJN452 - 0.15 mg qd	Pulse Rate	Day 21	72.5 bpm	Standard Deviation 6.75
LJN452 - 0.15 mg qd	Pulse Rate	Day 1	74.1 bpm	Standard Deviation 11.62
LJN452 - 0.15 mg qd	Pulse Rate	Day 28	67.2 bpm	Standard Deviation 3.42
LJN452 - 0.15 mg qd	Pulse Rate	Baseline	74.4 bpm	Standard Deviation 5.15
LJN452 - 0.15 mg qd	Pulse Rate	Day 84	72.8 bpm	Standard Deviation 8.12
LJN452 - 0.15 mg qd	Pulse Rate	Day 56	69.7 bpm	Standard Deviation 4.07
LJN452 - 0.15 mg qd	Pulse Rate	Screening	72.8 bpm	Standard Deviation 8.26
LJN452 - 0.15 mg qd	Pulse Rate	Day 14	75.1 bpm	Standard Deviation 6.74
Pooled Placebo	Pulse Rate	Screening	69.3 bpm	Standard Deviation 10.69
Pooled Placebo	Pulse Rate	Day 7	65.2 bpm	Standard Deviation 8.92
Pooled Placebo	Pulse Rate	Day 21	67.7 bpm	Standard Deviation 10.18
Pooled Placebo	Pulse Rate	Day 1	67.6 bpm	Standard Deviation 8.35
Pooled Placebo	Pulse Rate	Day 14	66.1 bpm	Standard Deviation 9.61
Pooled Placebo	Pulse Rate	Day 84	68.1 bpm	Standard Deviation 9.82
Pooled Placebo	Pulse Rate	Day 56	68.1 bpm	Standard Deviation 10.11
Pooled Placebo	Pulse Rate	Day 28	65.8 bpm	Standard Deviation 9.29
Pooled Placebo	Pulse Rate	Baseline	66.3 bpm	Standard Deviation 9.3

Secondary

Change From Baseline in Global Itch Visual Analogue Scale (VAS)

Baseline is defined as the latest available predose value. The Global Itch Visual Analogue Scale, a 100 mm visual analogue scale (VAS), was used to assess the severity of patients itch (ranging from 0 = none at all to 100 = the worst imaginable itch). The score range is between a minimum of 0 and a maximum of 100. The score (distance in mm from left) on the VAS was recorded by the patient marking with a line and used to test for an effect of tropifexor over placebo. The mean change from baseline in itch VAS score in each treatment group is presented.

Time frame: Day 7, Day 14, Day 21, Day 28, Day 56, and Day 84

Population: The PD analysis set included all subjects with any available PD data and no protocol deviations with relevant impact on PD data.

Arm	Measure	Group	Value (MEAN)
LJN452 - 0.03 mg qd	Change From Baseline in Global Itch Visual Analogue Scale (VAS)	Day 7	-2.04 mm
LJN452 - 0.03 mg qd	Change From Baseline in Global Itch Visual Analogue Scale (VAS)	Day 14	-8.04 mm
LJN452 - 0.03 mg qd	Change From Baseline in Global Itch Visual Analogue Scale (VAS)	Day 21	10.53 mm
LJN452 - 0.03 mg qd	Change From Baseline in Global Itch Visual Analogue Scale (VAS)	Day 28	8.62 mm
LJN452 - 0.03 mg qd	Change From Baseline in Global Itch Visual Analogue Scale (VAS)	Day 56	-7.81 mm
LJN452 - 0.03 mg qd	Change From Baseline in Global Itch Visual Analogue Scale (VAS)	Day 84	-5.14 mm
LJN452 - 0.06 mg qd	Change From Baseline in Global Itch Visual Analogue Scale (VAS)	Day 56	5.69 mm
LJN452 - 0.06 mg qd	Change From Baseline in Global Itch Visual Analogue Scale (VAS)	Day 84	0.89 mm
LJN452 - 0.06 mg qd	Change From Baseline in Global Itch Visual Analogue Scale (VAS)	Day 7	12.08 mm
LJN452 - 0.06 mg qd	Change From Baseline in Global Itch Visual Analogue Scale (VAS)	Day 21	19.54 mm
LJN452 - 0.06 mg qd	Change From Baseline in Global Itch Visual Analogue Scale (VAS)	Day 28	15.64 mm
LJN452 - 0.06 mg qd	Change From Baseline in Global Itch Visual Analogue Scale (VAS)	Day 14	13.77 mm
LJN452 - 0.09 mg qd	Change From Baseline in Global Itch Visual Analogue Scale (VAS)	Day 28	1.78 mm
LJN452 - 0.09 mg qd	Change From Baseline in Global Itch Visual Analogue Scale (VAS)	Day 56	-6.38 mm
LJN452 - 0.09 mg qd	Change From Baseline in Global Itch Visual Analogue Scale (VAS)	Day 7	14.66 mm
LJN452 - 0.09 mg qd	Change From Baseline in Global Itch Visual Analogue Scale (VAS)	Day 21	7.76 mm
LJN452 - 0.09 mg qd	Change From Baseline in Global Itch Visual Analogue Scale (VAS)	Day 14	6.51 mm
LJN452 - 0.09 mg qd	Change From Baseline in Global Itch Visual Analogue Scale (VAS)	Day 84	-6.44 mm
LJN452 - 0.15 mg qd	Change From Baseline in Global Itch Visual Analogue Scale (VAS)	Day 28	10.50 mm
LJN452 - 0.15 mg qd	Change From Baseline in Global Itch Visual Analogue Scale (VAS)	Day 14	14.20 mm
LJN452 - 0.15 mg qd	Change From Baseline in Global Itch Visual Analogue Scale (VAS)	Day 21	8.65 mm
LJN452 - 0.15 mg qd	Change From Baseline in Global Itch Visual Analogue Scale (VAS)	Day 84	-5.14 mm
LJN452 - 0.15 mg qd	Change From Baseline in Global Itch Visual Analogue Scale (VAS)	Day 56	-3.64 mm
LJN452 - 0.15 mg qd	Change From Baseline in Global Itch Visual Analogue Scale (VAS)	Day 7	27.45 mm
Pooled Placebo	Change From Baseline in Global Itch Visual Analogue Scale (VAS)	Day 56	7.44 mm
Pooled Placebo	Change From Baseline in Global Itch Visual Analogue Scale (VAS)	Day 21	2.74 mm
Pooled Placebo	Change From Baseline in Global Itch Visual Analogue Scale (VAS)	Day 14	6.03 mm
Pooled Placebo	Change From Baseline in Global Itch Visual Analogue Scale (VAS)	Day 84	11.79 mm
Pooled Placebo	Change From Baseline in Global Itch Visual Analogue Scale (VAS)	Day 28	1.59 mm
Pooled Placebo	Change From Baseline in Global Itch Visual Analogue Scale (VAS)	Day 7	0.74 mm

p-value: 0.98290% CI: [-14.38, 14.77]ANCOVA

p-value: 0.04790% CI: [-25.21, -2.43]ANCOVA

p-value: 0.02990% CI: [-31.81, -4.64]ANCOVA

p-value: 0.00490% CI: [11.97, 41.44]ANCOVA

p-value: 0.3790% CI: [-6.96, 23.29]ANCOVA

p-value: 0.55890% CI: [-10.86, 22.66]ANCOVA

p-value: 0.05490% CI: [-31.31, -2.54]ANCOVA

p-value: 0.18590% CI: [-2.78, 25.46]ANCOVA

p-value: 0.35190% CI: [-6.05, 21.52]ANCOVA

p-value: 0.05990% CI: [2.2, 31.38]ANCOVA

p-value: 0.13290% CI: [-1.35, 29.44]ANCOVA

p-value: 0.80990% CI: [-13.8, 10.31]ANCOVA

p-value: 0.2190% CI: [-25.29, 3.48]ANCOVA

p-value: 0.08690% CI: [0.58, 27.25]ANCOVA

p-value: 0.95190% CI: [-12.57, 13.53]ANCOVA

p-value: 0.54590% CI: [-8.79, 18.83]ANCOVA

p-value: 0.74390% CI: [-16.91, 11.34]ANCOVA

p-value: 0.09390% CI: [-27.85, -0.28]ANCOVA

p-value: 0.37690% CI: [-6.81, 22.38]ANCOVA

p-value: 0.44890% CI: [-8.36, 22.43]ANCOVA

p-value: 0.03990% CI: [-27.3, -3.19]ANCOVA

p-value: 0.41890% CI: [-9.34, 27.15]ANCOVA

p-value: 0.15690% CI: [-23.95, 1.8]ANCOVA

p-value: 0.06490% CI: [-31.94, -1.92]ANCOVA

Secondary

Change From Baseline in Itch Subdomain of PBC-40 Score

Baseline is defined as the latest available predose value. The PBC-40 is a paper-based, patient-derived, disease-specific health-related quality of life (HRQOL) patient reported outcome (PRO) measure which was developed and validated for use in PBC patients (Jacoby et al 2005). It consists of 40 questions arranged in 6 domains with between 3 and 11 questions in each domain. Each question is scored from 1 to 5 in increasing order of severity. This dataset focuses on the itch subdomain which consists of 3 questions. These 3 questions within the itch subdomain are summed to obtain a total score for the itch subdomain. The total score range is between a minimum of 3 and a maximum of 15. Higher scores represent a poorer quality of life. The median change from baseline in total itch subdomain score in each treatment group is presented.

Time frame: Baseline, Day 28, Day 56, Day 84

Population: The PD analysis set included all subjects with any available PD data and no protocol deviations with relevant impact on PD data.

Arm	Measure	Group	Value (MEDIAN)
LJN452 - 0.03 mg qd	Change From Baseline in Itch Subdomain of PBC-40 Score	Day 28	1.0 UNITS ON A SCALE
LJN452 - 0.03 mg qd	Change From Baseline in Itch Subdomain of PBC-40 Score	Day 84	0.0 UNITS ON A SCALE
LJN452 - 0.03 mg qd	Change From Baseline in Itch Subdomain of PBC-40 Score	Day 56	1.0 UNITS ON A SCALE
LJN452 - 0.06 mg qd	Change From Baseline in Itch Subdomain of PBC-40 Score	Day 56	1.0 UNITS ON A SCALE
LJN452 - 0.06 mg qd	Change From Baseline in Itch Subdomain of PBC-40 Score	Day 28	1.0 UNITS ON A SCALE
LJN452 - 0.06 mg qd	Change From Baseline in Itch Subdomain of PBC-40 Score	Day 84	0.0 UNITS ON A SCALE
LJN452 - 0.09 mg qd	Change From Baseline in Itch Subdomain of PBC-40 Score	Day 56	0.5 UNITS ON A SCALE
LJN452 - 0.09 mg qd	Change From Baseline in Itch Subdomain of PBC-40 Score	Day 28	2.0 UNITS ON A SCALE
LJN452 - 0.09 mg qd	Change From Baseline in Itch Subdomain of PBC-40 Score	Day 84	0.0 UNITS ON A SCALE
LJN452 - 0.15 mg qd	Change From Baseline in Itch Subdomain of PBC-40 Score	Day 28	2.0 UNITS ON A SCALE
LJN452 - 0.15 mg qd	Change From Baseline in Itch Subdomain of PBC-40 Score	Day 84	0.0 UNITS ON A SCALE
LJN452 - 0.15 mg qd	Change From Baseline in Itch Subdomain of PBC-40 Score	Day 56	0.0 UNITS ON A SCALE
Pooled Placebo	Change From Baseline in Itch Subdomain of PBC-40 Score	Day 56	0.0 UNITS ON A SCALE
Pooled Placebo	Change From Baseline in Itch Subdomain of PBC-40 Score	Day 28	0.0 UNITS ON A SCALE
Pooled Placebo	Change From Baseline in Itch Subdomain of PBC-40 Score	Day 84	0.0 UNITS ON A SCALE

p-value: 0.34290% CI: [-1, 2]Wilcoxon rank-sum test

p-value: 0.69990% CI: [-1, 2]Wilcoxon rank-sum test

p-value: 0.37790% CI: [-3, 0]Wilcoxon rank-sum test

p-value: 0.13290% CI: [0, 2]Wilcoxon rank-sum test

p-value: 0.29290% CI: [0, 2]Wilcoxon rank-sum test

p-value: 0.97990% CI: [-2, 1]Wilcoxon rank-sum test

p-value: 0.10290% CI: [0, 4]Wilcoxon rank-sum test

p-value: 0.71790% CI: [-1, 2]Wilcoxon rank-sum test

p-value: 190% CI: [-2, 1]Wilcoxon rank-sum test

p-value: 0.14290% CI: [0, 5]Wilcoxon rank-sum test

p-value: 0.97590% CI: [-1, 1]Wilcoxon rank-sum test

p-value: 0.60290% CI: [-2, 1]Wilcoxon rank-sum test

Secondary

Changes From Baseline in Total PBC-40 Score

Baseline is defined as the latest available predose value. The PBC-40 is a paper-based, patient-derived, disease-specific health-related quality of life (HRQOL) patient reported outcome (PRO) measure which was developed and validated for use in PBC patients (Jacoby et al 2005). It consists of 40 questions arranged in 6 domains with between 3 and 11 questions in each domain. Each question is scored from 1 to 5 in increasing order of severity. All questions within a domain are summed and all domain totals are summed to obtain a total score. The total score range is between a minimum of 40 and a maximum of 200. Higher scores represent a poorer quality of life. The median difference from baseline in total sum score for each treatment group is presented.

Time frame: Baseline, Day 28, Day 56, Day 84

Population: The PD analysis set included all subjects with any available PD data and no protocol deviations with relevant impact on PD data.

Arm	Measure	Group	Value (MEDIAN)
LJN452 - 0.03 mg qd	Changes From Baseline in Total PBC-40 Score	Day 28	2.0 units on a scale
LJN452 - 0.03 mg qd	Changes From Baseline in Total PBC-40 Score	Day 84	-2.0 units on a scale
LJN452 - 0.03 mg qd	Changes From Baseline in Total PBC-40 Score	Day 56	3.0 units on a scale
LJN452 - 0.06 mg qd	Changes From Baseline in Total PBC-40 Score	Day 56	3.0 units on a scale
LJN452 - 0.06 mg qd	Changes From Baseline in Total PBC-40 Score	Day 28	1.0 units on a scale
LJN452 - 0.06 mg qd	Changes From Baseline in Total PBC-40 Score	Day 84	-1.0 units on a scale
LJN452 - 0.09 mg qd	Changes From Baseline in Total PBC-40 Score	Day 56	-2.5 units on a scale
LJN452 - 0.09 mg qd	Changes From Baseline in Total PBC-40 Score	Day 28	3.5 units on a scale
LJN452 - 0.09 mg qd	Changes From Baseline in Total PBC-40 Score	Day 84	-3.5 units on a scale
LJN452 - 0.15 mg qd	Changes From Baseline in Total PBC-40 Score	Day 28	-1.0 units on a scale
LJN452 - 0.15 mg qd	Changes From Baseline in Total PBC-40 Score	Day 84	-1.0 units on a scale
LJN452 - 0.15 mg qd	Changes From Baseline in Total PBC-40 Score	Day 56	-3.0 units on a scale
Pooled Placebo	Changes From Baseline in Total PBC-40 Score	Day 56	1.0 units on a scale
Pooled Placebo	Changes From Baseline in Total PBC-40 Score	Day 28	-2.0 units on a scale
Pooled Placebo	Changes From Baseline in Total PBC-40 Score	Day 84	1.5 units on a scale

p-value: 0.89890% CI: [-7, 6]Wilcoxon rank-sum test

p-value: 0.59390% CI: [-4, 10]Wilcoxon rank-sum test

p-value: 0.50990% CI: [-11, 4]Wilcoxon rank-sum test

p-value: 0.59190% CI: [-5, 7]Wilcoxon rank-sum test

p-value: 0.70290% CI: [-12, 4]Wilcoxon rank-sum test

p-value: 0.83890% CI: [-10, 8]Wilcoxon rank-sum test

p-value: 0.29790% CI: [-3, 8]Wilcoxon rank-sum test

p-value: 0.23690% CI: [-14, 1]Wilcoxon rank-sum test

p-value: 0.19290% CI: [-15, 1]Wilcoxon rank-sum test

p-value: 0.60590% CI: [-2, 9]Wilcoxon rank-sum test

p-value: 0.03790% CI: [-21, -1]Wilcoxon rank-sum test

p-value: 0.39790% CI: [-11, 3]Wilcoxon rank-sum test

Secondary

Plasma PK Parameter - AUC 0-8h

Tropifexor levels were determined in plasma using a validated LC-MS/MS method. AUC0-t=The area under the plasma concentration-time curve from time zero to time 't' where t is a defined time point after administration \[mass x time / volume\]

Time frame: Day 1, Day 28

Population: The PK analysis set included all subjects with available PK data and no protocol deviations with relevant impact on PK data.

Arm	Measure	Group	Value (MEAN)	Dispersion
LJN452 - 0.03 mg qd	Plasma PK Parameter - AUC 0-8h	Day 28	7.95 hr*ng/mL	Standard Deviation 4.21
LJN452 - 0.03 mg qd	Plasma PK Parameter - AUC 0-8h	Day 1	4.98 hr*ng/mL	Standard Deviation 2.87
LJN452 - 0.06 mg qd	Plasma PK Parameter - AUC 0-8h	Day 28	17.6 hr*ng/mL	Standard Deviation 5.3
LJN452 - 0.06 mg qd	Plasma PK Parameter - AUC 0-8h	Day 1	12.1 hr*ng/mL	Standard Deviation 2.68
LJN452 - 0.09 mg qd	Plasma PK Parameter - AUC 0-8h	Day 28	23.4 hr*ng/mL	Standard Deviation 8.7
LJN452 - 0.15 mg qd	Plasma PK Parameter - AUC 0-8h	Day 1	24.5 hr*ng/mL	Standard Deviation 15.9
LJN452 - 0.15 mg qd	Plasma PK Parameter - AUC 0-8h	Day 28	44.2 hr*ng/mL	Standard Deviation 25.8

Secondary

Plasma PK Parameter - Cmax

Tropifexor levels were determined in plasma using a validated LC-MS/MS method. Cmax=The observed maximum plasma concentration following drug administration \[mass /volume\]

Time frame: Day 1, Day 28

Population: The PK analysis set included all subjects with available PK data and no protocol deviations with relevant impact on PK data.

Arm	Measure	Group	Value (MEAN)	Dispersion
LJN452 - 0.03 mg qd	Plasma PK Parameter - Cmax	Day 1	1.04 ng/mL	Standard Deviation 0.484
LJN452 - 0.03 mg qd	Plasma PK Parameter - Cmax	Day 28	1.25 ng/mL	Standard Deviation 0.559
LJN452 - 0.06 mg qd	Plasma PK Parameter - Cmax	Day 28	2.55 ng/mL	Standard Deviation 0.946
LJN452 - 0.06 mg qd	Plasma PK Parameter - Cmax	Day 1	1.80 ng/mL	Standard Deviation 0.585
LJN452 - 0.09 mg qd	Plasma PK Parameter - Cmax	Day 1	2.37 ng/mL	Standard Deviation 1.56
LJN452 - 0.09 mg qd	Plasma PK Parameter - Cmax	Day 28	4.30 ng/mL	Standard Deviation 2.1
LJN452 - 0.15 mg qd	Plasma PK Parameter - Cmax	Day 1	4.84 ng/mL	Standard Deviation 2.59
LJN452 - 0.15 mg qd	Plasma PK Parameter - Cmax	Day 28	6.37 ng/mL	Standard Deviation 3.4

Secondary

Plasma PK Parameter - Tmax

Tropifexor levels were determined in plasma using a validated LC-MS/MS method. Tmax = The time to reach the maximum concentration after drug administration \[time\]

Time frame: Day 1, Day 28

Population: The PK analysis set included all subjects with available PK data and no protocol deviations with relevant impact on PK data.

Arm	Measure	Group	Value (MEDIAN)
LJN452 - 0.03 mg qd	Plasma PK Parameter - Tmax	Day 1	4.12 hr
LJN452 - 0.03 mg qd	Plasma PK Parameter - Tmax	Day 28	4.08 hr
LJN452 - 0.06 mg qd	Plasma PK Parameter - Tmax	Day 28	4.00 hr
LJN452 - 0.06 mg qd	Plasma PK Parameter - Tmax	Day 1	4.00 hr
LJN452 - 0.09 mg qd	Plasma PK Parameter - Tmax	Day 1	4.00 hr
LJN452 - 0.09 mg qd	Plasma PK Parameter - Tmax	Day 28	4.00 hr
LJN452 - 0.15 mg qd	Plasma PK Parameter - Tmax	Day 1	4.00 hr
LJN452 - 0.15 mg qd	Plasma PK Parameter - Tmax	Day 28	5.00 hr

Source: ClinicalTrials.gov · Data processed: Feb 14, 2026

A Multi-part, Double Blind Study to Assess Safety, Tolerability and Efficacy of Tropifexor (LJN452) in PBC Patients

Conditions

Keywords

Brief summary

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Pre-assignment details

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Blood Pressure

Body Temperature

ECG - Heart Rate

ECG Intervals - PR Interval

Fold Change in Serum Gamma-glutamyl Transferase (GGT)

Haemoglobin

Pulse Rate

Change From Baseline in Global Itch Visual Analogue Scale (VAS)

Change From Baseline in Itch Subdomain of PBC-40 Score

Changes From Baseline in Total PBC-40 Score

Plasma PK Parameter - AUC 0-8h

Plasma PK Parameter - Cmax

Plasma PK Parameter - Tmax